There are about 100 billion neurons and 100 trillion synaptic connections between them in the human brain. The activity of those neural networks is controlled by only a handful of major neurotransmitters and all neurons respond to the excitatory transmitter glutamate and the inhibitory neurotransmitter GABA. This poses a major problem for using drugs that block or activate neurotransmitter receptors in understanding the function of specific circuits within and between brain regions and for treating neurological disorders. Ideally, the experimental neuroscientist wants to precisely control the activity of specific circuits of interest and the clinician wants to normalize the activity in dysfunctional circuits without altering the function of other circuits. Dr. Michael Tadross at Duke University has recently developed an ingenious solution to the problem of targeting selected neuron types with drugs – a technology called DART (drugs acutely targeted by tethering). In this episode Mike talks about his career path and how DART can be used to advance an understanding the function of specific neural circuits and may be used to restore brain function in disorders such as Parkinson's disease.

LINKS

Tadross laboratory: https://www.tadrosslab.com/tadross

Deconstructing behavioral neuropharmacology with cellular specificity: https://www-science-org.proxy1.library.jhu.edu/doi/epdf/10.1126/science.aaj2161

DART.2: bidirectional synaptic pharmacology with thousandfold cellular specificity.: file:///Users/markmattson/Downloads/s41592-024-02292-9.pdf

Natural phasic inhibition of dopamine neurons signals cognitive rigidity: https://pmc.ncbi.nlm.nih.gov/articles/PMC11100816/pdf/nihpp-2024.05.09.593320v2.pdf